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Model to study age-related macular degeneration could pave way for better treatment
Date:10/9/2007

PHILADELPHIA - Researchers at the University of Pennsylvania School of Medicine have created the first animal model of age-related macular degeneration (AMD) caused by a mutation known to produce disease in people, an important first step in developing treatments. The study appears in the October issue of Human Molecular Genetics.

Age-related macular degeneration is the most common cause of vision loss in elderly people, affecting more than 10 million people in the U.S. and about 50 million world-wide. Although it is a common and debilitating condition, prevention and treatment options are limited because AMD is a difficult condition to study.

To better develop treatments for preventing the progression of AMD, we need to understand the real biochemical details of how AMD occurs, says lead author Eric A. Pierce, MD, PhD, Associate Professor of Ophthalmology at Penns K.M Kirby Center for Molecular Ophthalmology. To do that, we need a model, and now we have one.

AMD is a difficult condition to investigate because it develops late in life patients typically show symptoms of AMD after 60, and the only samples researchers could use for study were from people who died while they had the early stages of AMD, and at that point, the tissue is not useful to study the conditions progression.

AMD is caused by the development of deposits between the retinal pigment epithelium and its basement membrane, called Bruchs membrane. The material starts as basal deposits and becomes drusen, extracellular deposits of protein and lipids that accumulate and can cause blindness. In order to prevent the basal deposits from forming, researchers need to understand the mechanisms that cause them to form in the first place.

By making this particular mutant mouse, weve made a model of early macular degeneration thats caused by a mutation we know produces macular degeneration in people, says Pierce. We think its going to be a good model to study the pathogenesis of basal deposits.

Some forms of macular degeneration are inherited, and one type is thought to be caused by a mutation in the Efemp1 gene. Pierce and colleagues created a mouse model of this inherited disorder by introducing the disease-causing mutation into the Efemp1 gene of mice. The resulting Efemp1-mutant mice develop the same basal deposits as people with AMD.

Pierce and colleagues plan to use the Efemp1-mutant mice to study how basal deposits form and what they are made of. The mice can also be used to test potential treatments to prevent basal deposit formation.


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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